RESUMO
While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.
Assuntos
Aquaporina 3/metabolismo , Camptotecina/análogos & derivados , Colo/metabolismo , Diarreia/prevenção & controle , Animais , Aquaporina 3/genética , Aquaporina 4/genética , Aquaporina 4/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Celecoxib/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diarreia/patologia , Diarreia/veterinária , Fezes/química , Expressão Gênica/efeitos dos fármacos , Irinotecano , Masculino , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Ratos , Ratos WistarRESUMO
Pneumatosis cystoides intestinalis (PCI) is a rare condition in which pneumocysts develop in the submucosa or subserosa of the colon. We report herein a case of PCI induced by the alpha-glucosidase inhibitor (alphaGI) miglitol. There have been 9 recorded cases of PCI induced by other alphaGIs, but this is the first report of miglitol causing PCI. The PCI lesions in our case were smaller than those induced by voglibose or acarbose. The possibility of PCI should be considered in diabetic patients on alphaGI therapy who complain of gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly investigated in these patients.